To Philippe and Francesco
26/05/10 19:14
I tried, several times, answering your comments to my blog posts, but I seem to be having trouble with that comment box. It jams up my computer and I can’t finish what I’m typing, once I start in that box.
Your comments and your questions are so interesting, though, they beg for a response. So, I will answer them here. You comments are listed as such, and my answers are below them:
Philippe
Melanie, don't forget I- and Br- (2 halogens). I- is not in big amount but, imporatnt to manage SCN.
2 days ago, 1:55:01 AM
Francesco
Hallo Melanie,
On this argument, i found that prof. Galietta from Italy have already understood some of the mechanisms. In the paper "Thiocyanate Transport in Resting and IL-4-Stimulated Human Bronchial Epithelial Cells: Role of Pendrin and Anion Channels" they found out that Cl- and SCN- are probably transported by the same protein, that they call Pendrin. This protein is stimulated by Interleukine4 (IL4) (a cytokine). this study underline again that SCN is important with lactoperoxydase as antibacterial system.
3 days ago, 2:53:39 PM
Francesco
This might be usefull:
http://www.jimmunol.org/cgi/content/full/181/7/4883 talks about what you illustrated us about the system LPO - SCN -H2O2 (the latter stimulated by IL-13 IL-4). And talks about pyocyanine produced by Pseudomonas.A. and its effect on the h2o2 depletion.
http://www.jimmunol.org/cgi/content/full/181/3/2203
this instead talks about the role of Pendrin in ASthma and the Role of stimulation of pendrin by Il-4 and by Il-13 on the ASL.
To Philippe, first: I was looking at an abstract, the other day, where the authors showed that iodide efflux via CFTR was increased in response to the LPS (a component of the bacterial wall) from the pathogen, PA. What is interesting is that the iodide efflux, under these conditions, is time and dose-dependent. See:
http://www.ncbi.nlm.nih.gov/pubmed/20346919
I had not paid much attention to iodide efflux previously, at all. Do you suppose that this is the purpose of it? To “manage” thiocyanate (SCN-)? If so, please explain this mechanism. The authors of the abstract linked above think it has something to do with phagocytosis.
To Francesco: The article that you refer to:
“Thiocyanate Transport in Resting and IL-4-Stimulated Human Bronchial Epithelial Cells: Role of Pendrin and Anion Channels” [J Immunol. 2007 Apr 15;178(8):5144-53 ] is not about the CFTR transport of thiocyanate. It refers to a different anion channel that the CFTR probably controls indirectly, from a family of transporters in the SLC26 class. See: EMBO J. 2002 Nov 1;21(21):5662-72. This is the same mechanism which controls HCO3- transport.
As to the second article you mentioned:
The Pseudomonas Toxin Pyocyanin Inhibits the Dual Oxidase-Based Antimicrobial System as It Imposes Oxidative Stress on Airway Epithelial Cells1 [The Journal of Immunology, 2008, 181, 4883 -4893],
the jury is still out on whether CF patients have not enough H2O2, or too much of it, and where this excess is located, ie., intracellular or extracellular. Look at this: PLoS One. 2008;3(10):e3367. “Dysfunction of Nrf-2 in CF epithelia leads to excess intracellular H2O2 and inflammatory cytokine production.” And this: Eur Respir J. 2000 Jul;16(1):95-100.
“Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment.”
I don’t agree that you can assume that pyocyanin, from PA, inhibits Duox enough to deprive lactoperoxidase of enough of it’s substrate (H2O2), to say that H2O2 and it’s precursor, superoxide anion, are not major contributors to the inflammatory component of this disease.
I can’t find it right this moment, but someone on Sharktank recently posted an article on the issue of whether infection or inflammation comes first in CF. And inflammation was the winner. I think that it is very important to remember that thiocyanate not only has antibacterial effects in it’s oxidized form (OSCN), but that unoxidized, it acts as a buffer for these oxidants.
Hey, on a side note, are you guys from Alaxia Biotech? Your names seem familiar….
Your comments and your questions are so interesting, though, they beg for a response. So, I will answer them here. You comments are listed as such, and my answers are below them:
Philippe
Melanie, don't forget I- and Br- (2 halogens). I- is not in big amount but, imporatnt to manage SCN.
2 days ago, 1:55:01 AM
Francesco
Hallo Melanie,
On this argument, i found that prof. Galietta from Italy have already understood some of the mechanisms. In the paper "Thiocyanate Transport in Resting and IL-4-Stimulated Human Bronchial Epithelial Cells: Role of Pendrin and Anion Channels" they found out that Cl- and SCN- are probably transported by the same protein, that they call Pendrin. This protein is stimulated by Interleukine4 (IL4) (a cytokine). this study underline again that SCN is important with lactoperoxydase as antibacterial system.
3 days ago, 2:53:39 PM
Francesco
This might be usefull:
http://www.jimmunol.org/cgi/content/full/181/7/4883 talks about what you illustrated us about the system LPO - SCN -H2O2 (the latter stimulated by IL-13 IL-4). And talks about pyocyanine produced by Pseudomonas.A. and its effect on the h2o2 depletion.
http://www.jimmunol.org/cgi/content/full/181/3/2203
this instead talks about the role of Pendrin in ASthma and the Role of stimulation of pendrin by Il-4 and by Il-13 on the ASL.
To Philippe, first: I was looking at an abstract, the other day, where the authors showed that iodide efflux via CFTR was increased in response to the LPS (a component of the bacterial wall) from the pathogen, PA. What is interesting is that the iodide efflux, under these conditions, is time and dose-dependent. See:
http://www.ncbi.nlm.nih.gov/pubmed/20346919
I had not paid much attention to iodide efflux previously, at all. Do you suppose that this is the purpose of it? To “manage” thiocyanate (SCN-)? If so, please explain this mechanism. The authors of the abstract linked above think it has something to do with phagocytosis.
To Francesco: The article that you refer to:
“Thiocyanate Transport in Resting and IL-4-Stimulated Human Bronchial Epithelial Cells: Role of Pendrin and Anion Channels” [J Immunol. 2007 Apr 15;178(8):5144-53 ] is not about the CFTR transport of thiocyanate. It refers to a different anion channel that the CFTR probably controls indirectly, from a family of transporters in the SLC26 class. See: EMBO J. 2002 Nov 1;21(21):5662-72. This is the same mechanism which controls HCO3- transport.
As to the second article you mentioned:
The Pseudomonas Toxin Pyocyanin Inhibits the Dual Oxidase-Based Antimicrobial System as It Imposes Oxidative Stress on Airway Epithelial Cells1 [The Journal of Immunology, 2008, 181, 4883 -4893],
the jury is still out on whether CF patients have not enough H2O2, or too much of it, and where this excess is located, ie., intracellular or extracellular. Look at this: PLoS One. 2008;3(10):e3367. “Dysfunction of Nrf-2 in CF epithelia leads to excess intracellular H2O2 and inflammatory cytokine production.” And this: Eur Respir J. 2000 Jul;16(1):95-100.
“Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment.”
I don’t agree that you can assume that pyocyanin, from PA, inhibits Duox enough to deprive lactoperoxidase of enough of it’s substrate (H2O2), to say that H2O2 and it’s precursor, superoxide anion, are not major contributors to the inflammatory component of this disease.
I can’t find it right this moment, but someone on Sharktank recently posted an article on the issue of whether infection or inflammation comes first in CF. And inflammation was the winner. I think that it is very important to remember that thiocyanate not only has antibacterial effects in it’s oxidized form (OSCN), but that unoxidized, it acts as a buffer for these oxidants.
Hey, on a side note, are you guys from Alaxia Biotech? Your names seem familiar….